[{"date_published":"2026-06-23T00:00:00Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","day":"23","oa":1,"PlanS_conform":"1","month":"06","date_updated":"2026-07-01T06:47:49Z","researchdata_availability":"yes","OA_type":"gold","dataavailabilitystatement":"Source data are provided with this paper. Additional original data are available from the corresponding author upon request. Code is available from https://doi.org/10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz","intvolume":"        17","acknowledgement":"We thank Jose Guzman, Simon Hippenmeyer, and Tim Vogels for critically reading the manuscript, Jozsef Csicsvari for useful discussions, Florian Marr for technical assistance, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA: the preclinical facility (PCF) provided housing and breeding of the animals, the imaging and optics facility (IOF) offered technical training and state of the art equipment, the Miba machine shop contributed to the construction and maintenance of multicellular recording setups, and the scientific computing unit helped with the large-scale simulations. The project received funding from the European Union’s Horizon 2020 research and innovation programme (ERC Advanced Grants No 692692 GIANTSYN and 101199096 CA3-SYNGRAM to P.J.; Marie Skłodowska-Curie Grant 754411 to V.V.B.; Marie Skłodowska-Curie Grant 101026635 to J.F.W.), the Fond zur Förderung der Wissenschaftlichen Forschung (P 36232-B, PAT4178023, and 10.55776/CoE16 to P.J.), and the Nomis Foundation (fellowship to A.N.-O.). V.V.B. received funding from a CONACyT fellowship (289638).","file_date_updated":"2026-07-01T06:46:06Z","abstract":[{"lang":"eng","text":"Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically preconfigured or environmentally shaped during ongoing memory storage is currently unknown. To address this question, we performed multicellular patch-clamp-based circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3 network undergoes a developmental transformation from local, dense, and random connectivity to a distributed, sparse, and structured configuration. Thus, sparse and structured connectivity may emerge via experience-dependent mechanisms. In parallel, the strength of single synapses is downregulated; single synaptic events are sufficient to trigger postsynaptic spiking early in development, whereas spatial summation of several inputs is required at later time points. Biologically inspired models of memory storage by Hebbian synaptic plasticity and retrieval via pattern completion suggest that developmental changes improve specific aspects of memory storage and retrieval. Our results imply a developmental transformation of the neuronal code and the memory functions in the hippocampal CA3 network.</jats:p>"}],"type":"journal_article","corr_author":"1","article_type":"original","author":[{"full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso","first_name":"Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823"},{"first_name":"Andrea C","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","full_name":"Navas Olivé, Andrea C","orcid":"0000-0002-9280-8597","last_name":"Navas Olivé"},{"orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois","last_name":"Schlögl","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2026-06-30T13:05:52Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"22229","related_material":{"record":[{"status":"public","relation":"research_data","id":"21442"}]},"status":"public","article_processing_charge":"Yes","supplementarymaterial":"yes","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"ec_funded":1,"doi":"10.1038/s41467-026-71914-x","ddc":["570"],"has_accepted_license":"1","license":"https://creativecommons.org/licenses/by/4.0/","das_tickbox":"1","publication_status":"published","title":"Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit","external_id":{"pmid":["42014695"]},"publication":"Nature Communications","publication_identifier":{"eissn":["2041-1723"]},"article_number":"5540","pmid":1,"OA_place":"publisher","DOAJ_listed":"1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"year":"2026","publisher":"Springer Nature","language":[{"iso":"eng"}],"volume":17,"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020"},{"grant_number":"101199096","_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"name":"Synaptic networks of human brain","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023"},{"_id":"26366136-B435-11E9-9278-68D0E5697425","name":"Reglas de Conectividad funcional en el hipocampo"}],"fulldoi":"https://doi.org/10.1038/s41467-026-71914-x","file":[{"content_type":"application/pdf","file_id":"22231","creator":"dernst","relation":"main_file","checksum":"d0b0093493926985b4c268662ff4d556","file_size":18304997,"date_updated":"2026-07-01T06:46:06Z","file_name":"2026_NatureComm_VargasBarroso.pdf","success":1,"date_created":"2026-07-01T06:46:06Z","access_level":"open_access"}],"oa_version":"Published Version","citation":{"ista":"Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. 2026. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature Communications. 17, 5540.","ieee":"V. M. Vargas Barroso, J. Watson, A. C. Navas Olivé, A. Schlögl, and P. M. Jonas, “Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026.","ama":"Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-71914-x\">10.1038/s41467-026-71914-x</a>","chicago":"Vargas Barroso, Victor M, Jake Watson, Andrea C Navas Olivé, Alois Schlögl, and Peter M Jonas. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/10.1038/s41467-026-71914-x</a>.","short":"V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas, Nature Communications 17 (2026).","apa":"Vargas Barroso, V. M., Watson, J., Navas Olivé, A. C., Schlögl, A., &#38; Jonas, P. M. (2026). Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/10.1038/s41467-026-71914-x</a>","mla":"Vargas Barroso, Victor M., et al. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” <i>Nature Communications</i>, vol. 17, 5540, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-71914-x\">10.1038/s41467-026-71914-x</a>."},"scopus_import":"1"},{"date_updated":"2026-07-01T06:47:49Z","has_accepted_license":"1","month":"03","doi":"10.15479/AT-ISTA-21442","day":"12","tmp":{"legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html","name":"GNU General Public License 3.0","short":"GPL 3.0"},"ec_funded":1,"oa":1,"department":[{"_id":"ScienComp"},{"_id":"PeJo"}],"date_published":"2026-03-12T00:00:00Z","file_date_updated":"2026-03-12T10:24:45Z","license":"https://opensource.org/licenses/GPL-3.0","title":"CA3Simu v1.06 (vargas2026v1)","author":[{"last_name":"Schlögl","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"}],"year":"2026","corr_author":"1","publisher":"Institute of Science and Technology Austria","keyword":["hypocampus","ca3 simulations","modelling"],"type":"software","citation":{"short":"A. Schlögl, (2026).","apa":"Schlögl, A. (2026). CA3Simu v1.06 (vargas2026v1). Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-21442\">https://doi.org/10.15479/AT-ISTA-21442</a>","mla":"Schlögl, Alois. <i>CA3Simu v1.06 (Vargas2026v1)</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-21442\">10.15479/AT-ISTA-21442</a>.","ista":"Schlögl A. 2026. CA3Simu v1.06 (vargas2026v1), Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT-ISTA-21442\">10.15479/AT-ISTA-21442</a>.","ieee":"A. Schlögl, “CA3Simu v1.06 (vargas2026v1).” Institute of Science and Technology Austria, 2026.","ama":"Schlögl A. CA3Simu v1.06 (vargas2026v1). 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-21442\">10.15479/AT-ISTA-21442</a>","chicago":"Schlögl, Alois. “CA3Simu v1.06 (Vargas2026v1).” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-21442\">https://doi.org/10.15479/AT-ISTA-21442</a>."},"project":[{"name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits","_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","grant_number":"101199096"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023","name":"Synaptic networks of human brain"},{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"}],"fulldoi":"https://doi.org/10.15479/AT-ISTA-21442","status":"public","file":[{"file_name":"ca3simu-vargas2026v1.tar.gz","date_updated":"2026-03-12T08:19:14Z","checksum":"441c8827717dcda05f91c127d15cf1e9","file_size":160410,"content_type":"application/gzip","file_id":"21443","creator":"schloegl","relation":"main_file","access_level":"open_access","success":1,"date_created":"2026-03-12T08:19:14Z"},{"creator":"schloegl","relation":"main_file","content_type":"text/markdown","file_id":"21445","file_size":10923,"checksum":"3c0092076228a15c0a7ae703192d43ea","file_name":"README.md","date_updated":"2026-03-12T10:24:45Z","date_created":"2026-03-12T10:24:45Z","success":1,"access_level":"open_access"}],"_id":"21442","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"22229"}]},"user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","date_created":"2026-03-12T08:20:46Z"},{"date_updated":"2026-08-04T09:29:55Z","PlanS_conform":"1","month":"06","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","day":"17","date_published":"2026-06-17T00:00:00Z","abstract":[{"lang":"eng","text":"Despite the functional diversity of over 100 causal genes1,2,3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD."}],"acknowledgement":"We thank F. Freeman, V. Voronin and M. Ladron de Guevara for technical assistance; A. Stichelberger and S. Liegenfeld for the management of our animal colony; M. Schunn, C. Gold and the Preclinical Facility team for technical assistance; C. Jansen and the Scientific Computing Facility for bioinformatics support and technical assistance; the Biomedical Sequencing Facility at CeMM for assistance with next-generation sequencing; and J. Lin and T. Krausgruber in the laboratory of C. Bock for support with flow cytometry; J. Kirchner for illustrating the multi-omics approach depicted in Fig. 1; and all members of the laboratory of G.N. for their support and discussions. This study was supported by the Scientific Service Units of ISTA through resources provided by the Imaging & Optics Facility and the Laboratory Support Facility. Bulk RNA-seq was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities, member of the Vienna BioCenter. This work was supported by a European Research Council Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the Austrian Science Fund (PE1028W1232 and PR1028FG1803) to G.N. Open access funding provided by Institute of Science and Technology (IST Austria).","dataavailabilitystatement":"Single-nucleus multiomics data are available from the Gene Expression Omnibus (GSE328363). The mm10 reference genome was used for the alignment (refdata-cellranger-arc-mm10-2020-A-2.0.0, obtained from https://cf.10xgenomics.com/supp/cell-arc/refdata-cellranger-arc-mm10-2020-A-2.0.0.tar.gz). Single-cell data can be accessed and visualized through a CELLxGENE database (https://adameykolab.hifo.meduniwien.ac.at/cellxgene_public/filecrawl/.2026_Nature_Schwarz). Source data are provided with this paper. Scripts and analyses that support the main findings of this study are accessible in a GitHub repository (https://git.ista.ac.at/research-sofware/mouseome).","OA_type":"hybrid","researchdata_availability":"yes","author":[{"first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","full_name":"Schwarz, Lena A"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"last_name":"Isaev","full_name":"Isaev, Sergey","first_name":"Sergey"},{"first_name":"Michela","id":"39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c","full_name":"Lisi, Michela","last_name":"Lisi"},{"last_name":"Malzl","full_name":"Malzl, Daniel","first_name":"Daniel"},{"last_name":"Büschl","full_name":"Büschl, Christoph","first_name":"Christoph","id":"2a8c054c-0913-11ee-9159-f8ef515809ed"},{"last_name":"Ladstätter","full_name":"Ladstätter, Sabrina","first_name":"Sabrina"},{"full_name":"Oliveira, Bárbara","last_name":"Oliveira","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Barel, Matteo","last_name":"Barel","first_name":"Matteo","id":"8959927b-2236-11ed-bd6e-ea83d94ade0e"},{"last_name":"Basilico","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette"},{"id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E","first_name":"Chaitanya","last_name":"Chintaluri","full_name":"Chintaluri, Chaitanya","orcid":"0000-0003-4252-1608"},{"first_name":"Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz","full_name":"Gorkiewicz, Sarah"},{"id":"3384113A-F248-11E8-B48F-1D18A9856A87","first_name":"Mohammad","full_name":"Goudarzi, Mohammad","last_name":"Goudarzi"},{"full_name":"Belinova, Tereza","last_name":"Belinova","first_name":"Tereza","id":"0bf89b6a-d28b-11eb-8bd6-f43768e4d368"},{"first_name":"Stephan","last_name":"Reichl","full_name":"Reichl, Stephan"},{"full_name":"Sendžikaitė, Gintarė","last_name":"Sendžikaitė","id":"dd6d52f2-c50d-11eb-9548-bcf0ff82b344","first_name":"Gintarė"},{"last_name":"Arcot Jayaram","full_name":"Arcot Jayaram, Satish","orcid":"0000-0002-2479-2669","id":"b0bbee33-09f7-11eb-909c-8b358058d28a","first_name":"Satish"},{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"last_name":"Vogels","full_name":"Vogels, Tim P","orcid":"0000-0003-3295-6181","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","first_name":"Tim P"},{"full_name":"Menche, Jörg","last_name":"Menche","first_name":"Jörg"},{"full_name":"Adameyko, Igor","last_name":"Adameyko","first_name":"Igor"},{"last_name":"Kharchenko","full_name":"Kharchenko, Peter Vasili","id":"0095641e-7eb7-11f1-8665-aec51a2ab5e0","first_name":"Peter Vasili"},{"last_name":"Bock","full_name":"Bock, Christoph","first_name":"Christoph"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"article_type":"original","corr_author":"1","type":"journal_article","supplementarymaterial":"yes","article_processing_charge":"Yes (via OA deal)","status":"public","related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/patterns-in-genetic-chaos/","relation":"press_release"}]},"_id":"22295","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2026-07-13T09:47:21Z","has_accepted_license":"1","ddc":["570"],"doi":"10.1038/s41586-026-10679-1","department":[{"_id":"AnKi"},{"_id":"GaNo"},{"_id":"TiVo"},{"_id":"ScienComp"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"PreCl"}],"publication":"Nature","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"external_id":{"pmid":["42310454"]},"title":"Cortical development dynamics across autism spectrum disorder mouse models","publication_status":"epub_ahead","publisher":"Springer Nature","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2026","pmid":1,"OA_place":"publisher","scopus_import":"1","citation":{"ieee":"L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.","ista":"Schwarz LA, Dotter C, Isaev S, Lisi M, Malzl D, Büschl C, Ladstätter S, Oliveira B, Barel M, Basilico B, Chintaluri C, Gorkiewicz S, Goudarzi M, Belinova T, Reichl S, Sendžikaitė G, Arcot Jayaram S, Koppensteiner P, Sommer CM, Vogels TP, Menche J, Adameyko I, Kharchenko PV, Bock C, Novarino G. 2026. Cortical development dynamics across autism spectrum disorder mouse models. Nature.","ama":"Schwarz LA, Dotter C, Isaev S, et al. Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>","chicago":"Schwarz, Lena A, Christoph Dotter, Sergey Isaev, Michela Lisi, Daniel Malzl, Christoph Büschl, Sabrina Ladstätter, et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>.","short":"L.A. Schwarz, C. Dotter, S. Isaev, M. Lisi, D. Malzl, C. Büschl, S. Ladstätter, B. Oliveira, M. Barel, B. Basilico, C. Chintaluri, S. Gorkiewicz, M. Goudarzi, T. Belinova, S. Reichl, G. Sendžikaitė, S. Arcot Jayaram, P. Koppensteiner, C.M. Sommer, T.P. Vogels, J. Menche, I. Adameyko, P.V. Kharchenko, C. Bock, G. Novarino, Nature (2026).","apa":"Schwarz, L. A., Dotter, C., Isaev, S., Lisi, M., Malzl, D., Büschl, C., … Novarino, G. (2026). Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>","mla":"Schwarz, Lena A., et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>."},"oa_version":"Published Version","project":[{"_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","grant_number":"101044865","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neurobiology of anxiety in autism spectrum disorders","_id":"ebb38b5d-77a9-11ec-83b8-a42e08120a88","grant_number":"FG1803 49015"}],"fulldoi":"https://doi.org/10.1038/s41586-026-10679-1","main_file_link":[{"url":"https://doi.org/10.1038/s41586-026-10679-1","open_access":"1"}],"language":[{"iso":"eng"}]},{"date_updated":"2026-09-22T06:56:26Z","PlanS_conform":"1","month":"07","day":"01","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","oa":1,"date_published":"2026-07-01T00:00:00Z","acknowledgement":"We thank the scientific service units at ISTA, especially the imaging optic facility (IOF), the machine shop (Miba), specifically T. Asenov, the preclinical facility (PCF), specifically M. Schunn and S. Haslinger, C. Jansen for bioinformatic support, and the laboratory support facility (LSF). We also thank M. Benevento for supporting the design and partial performance of electrophysiology and fluorescence in situ hybridization experiments and for extensive discussions about the manuscript draft, R. Schulz and G. Colombo for advice on morphological reconstruction, M. Schmidt for valuable discussions about Fkbp5, and all Siegert team members for constant feedback on the project and manuscript. Grammarly was used to assist with grammatical revisions. We specifically acknowledge the following experimental contributions: R.J.A.C. (Multiome quality control), P.K. (electrophysiology), B.T., C.T.J.V., K.J. (multiome), J.Y. (KXA estimates), M.A. and T.N. (morphOMICs).\r\nA.V., M.A., T.N., R.J.A.C., J.Y., P.K., and S.S. were supported by the Institute of Science and Technology Austria. C.T.J.V., K.J., and B.T. were supported by the Allen Institute.","intvolume":"        12","file_date_updated":"2026-09-22T06:50:16Z","abstract":[{"text":"Anesthesia recovery is critical for resuming normal physiological and neuronal functions; however, the mechanisms involved remain elusive. Here, we identify a female-selective corticosterone-mediated microglia-neuron interaction during ketamine anesthesia recovery, absent in males. This microglia-neuron interaction induces plastic and functional neuronal changes, as evidenced by increased mEPSC frequency, which was occluded upon microglia depletion. We showed that this process is driven through up-regulation of the stress-responsive co-chaperone Fkbp5 mRNA and its protein, Fkbp51, in female microglia. Fkbp5/Fkbp51 is a key intermediary in a corticosteroid-induced stress response, and its involvement points toward a critical interface between endocrine signaling and microglia. To counteract the observed ketamine anesthesia-mediated increase in blood corticosterone during recovery, we removed the primary source of corticosterone by adrenalectomy. Close microglia-neuron interaction was reduced and increased again following corticosterone injection. Our findings identify a sex-specific microglia-mediated mechanism of neuronal plasticity during anesthesia recovery, driven by corticosterone, thereby enhancing our understanding of sex differences in brain function.","lang":"eng"}],"dataavailabilitystatement":"All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. This study did not generate new materials. Transcriptional data can be accessed at the NCBI GEO accession GSE298669. The code for the morphological analysis is available under DOI: https://doi.org/10.5281/zenodo.19057068. The codes for the single-nucleus analysis are accessible under DOI: 10.5281/zenodo.19019013 and DOI: 10.5281/zenodo.19071467.","OA_type":"gold","researchdata_availability":"yes","author":[{"last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro"},{"id":"65a3f615-b651-11f1-9c4b-da4396a4174a","first_name":"Amin","last_name":"Alam","full_name":"Alam, Amin"},{"first_name":"Thomas","id":"37d68bf2-b651-11f1-b680-ec86ff9a70f3","full_name":"Negrello, Thomas","last_name":"Negrello"},{"last_name":"Jin","full_name":"Jin, Kelly","first_name":"Kelly"},{"full_name":"van Velthoven, Cindy T. J.","last_name":"van Velthoven","first_name":"Cindy T. J."},{"full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero","first_name":"Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425"},{"orcid":"0000-0003-1732-1559","full_name":"Yeung, Jake","last_name":"Yeung","id":"123012b2-db30-11eb-b4d8-a35840c0551b","first_name":"Jake"},{"first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948"},{"full_name":"Tasic, Bosiljka","last_name":"Tasic","first_name":"Bosiljka"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra"}],"corr_author":"1","article_type":"original","type":"journal_article","issue":"31","article_processing_charge":"Yes","supplementarymaterial":"yes","status":"public","_id":"22951","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2026-09-17T11:05:39Z","has_accepted_license":"1","doi":"10.1126/sciadv.adz6517","ddc":["570"],"department":[{"_id":"SaSi"},{"_id":"ScienComp"},{"_id":"PreCl"}],"publication":"Science Advances","publication_identifier":{"eissn":["2375-2548"]},"article_number":"eadz6517","external_id":{"pmid":["42536755 "]},"das_tickbox":"1","publication_status":"published","title":"Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia","year":"2026","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"LifeSc"}],"publisher":"AAAS","DOAJ_listed":"1","OA_place":"publisher","pmid":1,"scopus_import":"1","citation":{"chicago":"Venturino, Alessandro, Amin Alam, Thomas Negrello, Kelly Jin, Cindy T. J. van Velthoven, Ryan J Cubero, Jake Yeung, Peter Koppensteiner, Bosiljka Tasic, and Sandra Siegert. “Corticosterone-Linked Microglial Activity Underpins Sexually Dimorphic Neuroplasticity after Ketamine Anesthesia.” <i>Science Advances</i>. AAAS, 2026. <a href=\"https://doi.org/10.1126/sciadv.adz6517\">https://doi.org/10.1126/sciadv.adz6517</a>.","ama":"Venturino A, Alam A, Negrello T, et al. Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia. <i>Science Advances</i>. 2026;12(31). doi:<a href=\"https://doi.org/10.1126/sciadv.adz6517\">10.1126/sciadv.adz6517</a>","ieee":"A. Venturino <i>et al.</i>, “Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia,” <i>Science Advances</i>, vol. 12, no. 31. AAAS, 2026.","ista":"Venturino A, Alam A, Negrello T, Jin K, van Velthoven CTJ, Cubero RJ, Yeung J, Koppensteiner P, Tasic B, Siegert S. 2026. Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia. Science Advances. 12(31), eadz6517.","mla":"Venturino, Alessandro, et al. “Corticosterone-Linked Microglial Activity Underpins Sexually Dimorphic Neuroplasticity after Ketamine Anesthesia.” <i>Science Advances</i>, vol. 12, no. 31, eadz6517, AAAS, 2026, doi:<a href=\"https://doi.org/10.1126/sciadv.adz6517\">10.1126/sciadv.adz6517</a>.","apa":"Venturino, A., Alam, A., Negrello, T., Jin, K., van Velthoven, C. T. J., Cubero, R. J., … Siegert, S. (2026). Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia. <i>Science Advances</i>. AAAS. <a href=\"https://doi.org/10.1126/sciadv.adz6517\">https://doi.org/10.1126/sciadv.adz6517</a>","short":"A. Venturino, A. Alam, T. Negrello, K. Jin, C.T.J. van Velthoven, R.J. Cubero, J. Yeung, P. Koppensteiner, B. Tasic, S. Siegert, Science Advances 12 (2026)."},"oa_version":"Published Version","fulldoi":"https://doi.org/10.1126/sciadv.adz6517","file":[{"access_level":"open_access","date_created":"2026-09-22T06:50:16Z","success":1,"checksum":"715a1f35a0805be85ef90556205a2cbc","file_size":4556377,"file_name":"2026_ScienceAdv_Venturino.pdf","date_updated":"2026-09-22T06:50:16Z","creator":"dernst","relation":"main_file","file_id":"22980","content_type":"application/pdf"}],"volume":12,"language":[{"iso":"eng"}]},{"article_processing_charge":"No","status":"public","_id":"21920","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_created":"2026-05-27T06:54:04Z","author":[{"first_name":"Yuri","last_name":"Ignatyev","full_name":"Ignatyev, Yuri"},{"full_name":"Papadopoulos, Stavros","last_name":"Papadopoulos","id":"40606b92-f128-11eb-9611-bf66a98cfa5c","first_name":"Stavros"},{"full_name":"Soretić, Mateja","last_name":"Soretić","first_name":"Mateja"},{"id":"123012b2-db30-11eb-b4d8-a35840c0551b","first_name":"Jake","last_name":"Yeung","full_name":"Yeung, Jake","orcid":"0000-0003-1732-1559"},{"first_name":"Tzi-Yang","full_name":"Lin, Tzi-Yang","last_name":"Lin"},{"first_name":"Elly M","last_name":"Tanaka","full_name":"Tanaka, Elly M"},{"first_name":"Leonid","full_name":"Peshkin, Leonid","last_name":"Peshkin"},{"first_name":"Ariel J","full_name":"Levine, Ariel J","last_name":"Levine"},{"first_name":"Mariano I","full_name":"Gabitto, Mariano I","last_name":"Gabitto"},{"id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","first_name":"Lora Beatrice Jaeger","last_name":"Sweeney","orcid":"0000-0001-9242-5601","full_name":"Sweeney, Lora Beatrice Jaeger"}],"corr_author":"1","type":"preprint","abstract":[{"text":"Vertebrates display remarkable diversity of sensorimotor behaviors, each adapted to distinct ecological and survival demands. This diversity raises fundamental questions about the evolutionary origin of motor control: do conserved spinal circuits underlie these behaviors, and how have they diverged across species. Recent studies detail spinal cell-type architecture in mammals but comparable, high-resolution atlases of the non-mammalian spinal cord are lacking. Here, we compare spinal cord cell types between fish, frogs, mice and humans, spanning ∼450 million years of evolution. Across species, we define highly conserved programs of cell type specification that segregate spinal neurons into nearly identical cardinal classes during development. This contrasts with adult stages, when spinal cell-type composition selectively diverges for excitatory neuron subpopulations. Using spatial transcriptomics, we localize this species divergence to the superficial, dorsal spinal cord, where variant neuropeptide expression defines mammalian-specific cell types. The most dorsal spinal cord thus emerges as a recently evolved hub for sensory integration in mammals, a neospinal cord analogous to the neocortex.</jats:p>","lang":"eng"}],"acknowledgement":"We would like to thank the members of the Sweeney Lab for discussion and support; Andrey\r\nBydanov for technical assistance with single-cell sequencing processing; and Jay Bikoff,\r\nNikos Konstantinides, Maria Tosches, and Graziana Gatto for comments on the manuscript. \r\nThis research was supported by: Horizon Europe ERC Starting Grant 101041551 (L.B.S,\r\nY.I., S.P.); Special Research Program (SFB) of the Austrian Science Fund (FWF) F7814-B\r\n(L.B.S., S.P., E.M.T); Austrian Science Fund (FWF) 10.55776/COE16 (L.B.S., Y.I., E.M.T.);\r\nAustrian Academy of Sciences DOC Fellowship 27229 (S.P.); ERC Advanced Grant 742046\r\n(E.M.T.); NIH award R24 OD031956 (L.P.); and in part by the Intramural Research\r\nProgram of the National Institutes of Health (NIH) through 1ZIA NS003153 to A.J.L.\r\nThe contributions of the NIH author are considered Works of the United States\r\nGovernment. The findings and conclusions presented in this paper are those of\r\nthe authors and do not necessarily reflect the views of the NIH or the U.S. Department\r\nof Health and Human Services. ","OA_type":"green","date_updated":"2026-05-27T07:25:41Z","month":"10","oa":1,"day":"11","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"date_published":"2025-10-11T00:00:00Z","oa_version":"Preprint","citation":{"chicago":"Ignatyev, Yuri, Stavros Papadopoulos, Mateja Soretić, Jake Yeung, Tzi-Yang Lin, Elly M Tanaka, Leonid Peshkin, Ariel J Levine, Mariano I Gabitto, and Lora B. Sweeney. “Innovations in Spinal Cord Cell Type Heterogeneity across Vertebrate Evolution.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2025.10.09.680955\">https://doi.org/10.1101/2025.10.09.680955</a>.","ama":"Ignatyev Y, Papadopoulos S, Soretić M, et al. Innovations in spinal cord cell type heterogeneity across vertebrate evolution. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2025.10.09.680955\">10.1101/2025.10.09.680955</a>","ieee":"Y. Ignatyev <i>et al.</i>, “Innovations in spinal cord cell type heterogeneity across vertebrate evolution,” <i>bioRxiv</i>. .","ista":"Ignatyev Y, Papadopoulos S, Soretić M, Yeung J, Lin T-Y, Tanaka EM, Peshkin L, Levine AJ, Gabitto MI, Sweeney LB. Innovations in spinal cord cell type heterogeneity across vertebrate evolution. bioRxiv, <a href=\"https://doi.org/10.1101/2025.10.09.680955\">10.1101/2025.10.09.680955</a>.","short":"Y. Ignatyev, S. Papadopoulos, M. Soretić, J. Yeung, T.-Y. Lin, E.M. Tanaka, L. Peshkin, A.J. Levine, M.I. Gabitto, L.B. Sweeney, BioRxiv (n.d.).","mla":"Ignatyev, Yuri, et al. “Innovations in Spinal Cord Cell Type Heterogeneity across Vertebrate Evolution.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2025.10.09.680955\">10.1101/2025.10.09.680955</a>.","apa":"Ignatyev, Y., Papadopoulos, S., Soretić, M., Yeung, J., Lin, T.-Y., Tanaka, E. M., … Sweeney, L. B. (n.d.). Innovations in spinal cord cell type heterogeneity across vertebrate evolution. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2025.10.09.680955\">https://doi.org/10.1101/2025.10.09.680955</a>"},"project":[{"_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","grant_number":"101041551","name":"Development and Evolution of Tetrapod Motor Circuits"},{"grant_number":"27229","_id":"907b765e-16d5-11f0-9cad-fef108a945b1","name":"A Tale of Two Circuits: Rostrocaudal spinal cord patterning during the swim-to-limb transition of Xenopus metamorphosis"}],"fulldoi":"https://doi.org/10.1101/2025.10.09.680955","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.10.09.680955"}],"language":[{"iso":"eng"}],"year":"2025","OA_place":"repository","publication":"bioRxiv","title":"Innovations in spinal cord cell type heterogeneity across vertebrate evolution","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","publication_status":"submitted","doi":"10.1101/2025.10.09.680955","department":[{"_id":"LoSw"},{"_id":"ScienComp"}]},{"date_published":"2024-06-13T00:00:00Z","oa":1,"day":"13","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","month":"06","date_updated":"2024-06-17T09:40:37Z","file_date_updated":"2024-06-17T09:36:51Z","type":"conference_abstract","conference":{"location":"Grundlsee, Austria","name":"ASHPC: Austrian-Slovenian HPC Meeting","end_date":"2024-06-13","start_date":"2024-06-10"},"page":"46","author":[{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","last_name":"Schlögl","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois"},{"id":"097c0562-3cf0-11ee-8fd3-e7a79c1e2fd1","first_name":"Waleed","last_name":"Khalid","full_name":"Khalid, Waleed"},{"full_name":"Elefante, Stefano","last_name":"Elefante","id":"490F40CE-F248-11E8-B48F-1D18A9856A87","first_name":"Stefano"},{"full_name":"Stadlbauer, Stephan","last_name":"Stadlbauer","id":"4D0BC184-F248-11E8-B48F-1D18A9856A87","first_name":"Stephan"}],"date_created":"2024-06-14T09:06:36Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"17139","status":"public","article_processing_charge":"No","department":[{"_id":"ScienComp"}],"ddc":["000"],"doi":"10.25365/phaidra.463","has_accepted_license":"1","title":"How much memory per CPU core is requested?","publication_status":"published","publication_identifier":{"isbn":["9783200096455"]},"publication":"ASHPC24 - Austrian-Slovenian HPC Meeting 2024","publisher":"EuroCC Austria","year":"2024","language":[{"iso":"eng"}],"file":[{"file_size":206746,"checksum":"f7d3dded6df2dcdb4818904cf2e1c183","file_name":"2024_ASHPC_Schloegl.pdf","date_updated":"2024-06-17T09:36:51Z","file_id":"17153","content_type":"application/pdf","creator":"dernst","relation":"main_file","access_level":"open_access","success":1,"date_created":"2024-06-17T09:36:51Z"}],"fulldoi":"https://doi.org/10.25365/phaidra.463","citation":{"ama":"Schlögl A, Khalid W, Elefante S, Stadlbauer S. How much memory per CPU core is requested? In: <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>. EuroCC Austria; 2024:46. doi:<a href=\"https://doi.org/10.25365/phaidra.463\">10.25365/phaidra.463</a>","chicago":"Schlögl, Alois, Waleed Khalid, Stefano Elefante, and Stephan Stadlbauer. “How Much Memory per CPU Core Is Requested?” In <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>, 46. EuroCC Austria, 2024. <a href=\"https://doi.org/10.25365/phaidra.463\">https://doi.org/10.25365/phaidra.463</a>.","ista":"Schlögl A, Khalid W, Elefante S, Stadlbauer S. 2024. How much memory per CPU core is requested? ASHPC24 - Austrian-Slovenian HPC Meeting 2024. ASHPC: Austrian-Slovenian HPC Meeting, 46.","ieee":"A. Schlögl, W. Khalid, S. Elefante, and S. Stadlbauer, “How much memory per CPU core is requested?,” in <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>, Grundlsee, Austria, 2024, p. 46.","mla":"Schlögl, Alois, et al. “How Much Memory per CPU Core Is Requested?” <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>, EuroCC Austria, 2024, p. 46, doi:<a href=\"https://doi.org/10.25365/phaidra.463\">10.25365/phaidra.463</a>.","apa":"Schlögl, A., Khalid, W., Elefante, S., &#38; Stadlbauer, S. (2024). How much memory per CPU core is requested? In <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i> (p. 46). Grundlsee, Austria: EuroCC Austria. <a href=\"https://doi.org/10.25365/phaidra.463\">https://doi.org/10.25365/phaidra.463</a>","short":"A. Schlögl, W. Khalid, S. Elefante, S. Stadlbauer, in:, ASHPC24 - Austrian-Slovenian HPC Meeting 2024, EuroCC Austria, 2024, p. 46."},"oa_version":"Published Version"},{"month":"07","date_updated":"2026-10-02T11:21:19Z","date_published":"2024-07-01T00:00:00Z","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"day":"01","quality_controlled":"1","abstract":[{"lang":"eng","text":"Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses."}],"file_date_updated":"2024-07-22T11:27:22Z","acknowledgement":"We thank A. Bergthaler (Research Center for Molecular Medicine of the Austrian Academy of Sciences) for providing VACV WR. We thank A. Nicholas and his team at the ISTA proteomics facility, and S. Elefante at the ISTA Scientific Computing facility for their support. We also thank F. Fäßler, D. Porley, T. Muthspiel and other members of the Schur group for support and helpful discussions. We also thank D. Castaño-Díez for support with Dynamo. We thank D. Farrell for his help optimizing the Rosetta protocol to refine the atomic model into the cryo-EM map with symmetry.\r\n\r\nF.K.M.S. acknowledges support from ISTA and EMBO. F.K.M.S. also received support from the Austrian Science Fund (FWF) grant P31445. This publication has been made possible in part by CZI grant DAF2021-234754 and grant https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989) awarded to F.K.M.S.\r\n\r\nThis research was also supported by the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We also acknowledge the use of COSMIC45 and Colabfold46.","intvolume":"        31","researchdata_availability":"yes","OA_type":"hybrid","dataavailabilitystatement":"The electron microscopy density maps of the A10 trimer and the hexameric flower-shaped pore, the subtomogram average of the palisade layer and representative tomograms for complete viruses as well as isolated cores have been deposited in the Electron Microscopy Data Bank under accession codes: EMD-17410, EMD-17411, EMD-17412, EMD-17413, EMD-17414 and EMD-18452.\r\n\r\nThe refined model of the A10 trimer has been deposited in the Protein Data Bank accession code: PDB 8P4K.\r\n\r\nThe UniProt codes of VACV core proteins used for structure prediction are: A10 (P16715), A3 (P06440), A4 (P29191) and L4 (P03295).\r\n\r\nGenBank Protein IDs of variola virus A10 (ABF23487.1), monkeypox virus A10 (YP_010377118.1), rabbitpox virus A10 (AAS49831.1), cowpox virus A10 (ADZ29251.1), ectromelia virus A10 (NP_671631.1), orf virus P4a (AY386264.1), Amsacta moorei entomopoxvirus AMV139 (NP_064921.1) and Melanoplus sanguinipes entomopoxvirus putative core protein P4a homolog (AF063866.1) were used for protein sequence alignment. Source data for MS experiments are provided as Supplementary Information accompanying this manuscript.","corr_author":"1","article_type":"original","page":"1114-1123","author":[{"full_name":"Datler, Julia","orcid":"0000-0002-3616-8580","last_name":"Datler","first_name":"Julia","id":"3B12E2E6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hansen","full_name":"Hansen, Jesse","orcid":"0000-0001-7967-2085","id":"1063c618-6f9b-11ec-9123-f912fccded63","first_name":"Jesse"},{"first_name":"Andreas","id":"3A18A7B8-F248-11E8-B48F-1D18A9856A87","last_name":"Thader","full_name":"Thader, Andreas"},{"first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","last_name":"Schlögl"},{"last_name":"Bauer","full_name":"Bauer, Lukas W","id":"0c894dcf-897b-11ed-a09c-8186353224b0","first_name":"Lukas W"},{"orcid":"0000-0003-3904-947X","full_name":"Hodirnau, Victor-Valentin","last_name":"Hodirnau","first_name":"Victor-Valentin","id":"3661B498-F248-11E8-B48F-1D18A9856A87"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","first_name":"Florian KM","last_name":"Schur","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078"}],"isi":1,"type":"journal_article","status":"public","supplementarymaterial":"yes","article_processing_charge":"Yes (in subscription journal)","date_created":"2024-02-12T09:59:45Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"18766"}],"link":[{"description":"News on ISTA Website","url":"https://ista.ac.at/en/news/down-to-the-core-of-poxviruses/","relation":"press_release"}]},"_id":"14979","ddc":["570"],"APC_amount":"11700 EUR","doi":"10.1038/s41594-023-01201-6","has_accepted_license":"1","department":[{"_id":"FlSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"publication":"Nature Structural & Molecular Biology","publication_identifier":{"eissn":["1545-9985"],"issn":["1545-9993"]},"title":"Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores","publication_status":"published","das_tickbox":"1","external_id":{"isi":["001158144600002"],"pmid":["38316877"]},"publisher":"Springer Nature","year":"2024","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"pmid":1,"OA_place":"publisher","keyword":["Molecular Biology","Structural Biology"],"file":[{"content_type":"application/pdf","file_id":"17307","creator":"dernst","relation":"main_file","file_name":"2024_NatureStrucBio_Datler.pdf","date_updated":"2024-07-22T11:27:22Z","checksum":"bda7bf65d81455480efaed8ca293b0db","file_size":17485494,"success":1,"date_created":"2024-07-22T11:27:22Z","access_level":"open_access"}],"project":[{"call_identifier":"FWF","name":"Structural conservation and diversity in retroviral capsid","grant_number":"P31445","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"fulldoi":"https://doi.org/10.1038/s41594-023-01201-6","citation":{"ista":"Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK. 2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural &#38; Molecular Biology. 31, 1114–1123.","ieee":"J. Datler <i>et al.</i>, “Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 31. Springer Nature, pp. 1114–1123, 2024.","chicago":"Datler, Julia, Jesse Hansen, Andreas Thader, Alois Schlögl, Lukas W Bauer, Victor-Valentin Hodirnau, and Florian KM Schur. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>.","ama":"Datler J, Hansen J, Thader A, et al. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. 2024;31:1114-1123. doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>","short":"J. Datler, J. Hansen, A. Thader, A. Schlögl, L.W. Bauer, V.-V. Hodirnau, F.K. Schur, Nature Structural &#38; Molecular Biology 31 (2024) 1114–1123.","apa":"Datler, J., Hansen, J., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V., &#38; Schur, F. K. (2024). Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>","mla":"Datler, Julia, et al. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 31, Springer Nature, 2024, pp. 1114–23, doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>."},"oa_version":"Published Version","scopus_import":"1","language":[{"iso":"eng"}],"volume":31},{"intvolume":"        41","acknowledgement":"We thank M. van Loenhout for experimental advice on purifying cell types from the bone marrow, R. van der Linden for expertise with FACS and M. Blotenburg for help with cell typing the mouse organogenesis dataset. We thank M. Saraswat and O. Stegle for discussions on multinomial distributions. This work was supported by a European Research Council Advanced grant (ERC-AdG 742225-IntScOmics); Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP grant (NWO CW 714.016.001) and NWO grant (OCENW.GROOT.2019.017); the Swiss National Science Foundation Early Postdoc Mobility (P2ELP3-184488 to P.Z. and P2BSP3-174991 to J.Y.); Marie Sklodowska-Curie Actions Postdoc (798573 to P.Z.) and the Human Frontier for Science Program Long-Term Fellowships (LT000209-2018-L to P.Z. and LT000097-2019-L to J.Y.). This work is part of the Oncode Institute which is financed partly by the Dutch Cancer Society.","file_date_updated":"2023-08-16T11:30:45Z","abstract":[{"text":"Regulation of chromatin states involves the dynamic interplay between different histone modifications to control gene expression. Recent advances have enabled mapping of histone marks in single cells, but most methods are constrained to profile only one histone mark per cell. Here, we present an integrated experimental and computational framework, scChIX-seq (single-cell chromatin immunocleavage and unmixing sequencing), to map several histone marks in single cells. scChIX-seq multiplexes two histone marks together in single cells, then computationally deconvolves the signal using training data from respective histone mark profiles. This framework learns the cell-type-specific correlation structure between histone marks, and therefore does not require a priori assumptions of their genomic distributions. Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single cells across a range of mark combinations. Modeling dynamics of in vitro macrophage differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq unlocks systematic interrogation of the interplay between histone modifications in single cells.","lang":"eng"}],"month":"06","date_updated":"2025-04-23T08:45:24Z","date_published":"2023-06-01T00:00:00Z","quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"day":"01","oa":1,"status":"public","article_processing_charge":"No","date_created":"2023-01-08T23:00:53Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12106","article_type":"original","corr_author":"1","page":"813–823","author":[{"full_name":"Yeung, Jake","orcid":"0000-0003-1732-1559","last_name":"Yeung","id":"123012b2-db30-11eb-b4d8-a35840c0551b","first_name":"Jake"},{"first_name":"Maria","full_name":"Florescu, Maria","last_name":"Florescu"},{"first_name":"Peter","full_name":"Zeller, Peter","last_name":"Zeller"},{"full_name":"De Barbanson, Buys Anton","last_name":"De Barbanson","first_name":"Buys Anton"},{"last_name":"Wellenstein","full_name":"Wellenstein, Max D.","first_name":"Max D."},{"last_name":"Van Oudenaarden","full_name":"Van Oudenaarden, Alexander","first_name":"Alexander"}],"type":"journal_article","isi":1,"publication":"Nature Biotechnology","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"publication_status":"published","title":"scChIX-seq infers dynamic relationships between histone modifications in single cells","external_id":{"isi":["000909067600003"],"pmid":["36593403"]},"doi":"10.1038/s41587-022-01560-3","ddc":["570"],"has_accepted_license":"1","department":[{"_id":"ScienComp"}],"fulldoi":"https://doi.org/10.1038/s41587-022-01560-3","file":[{"relation":"main_file","creator":"dernst","content_type":"application/pdf","file_id":"14066","file_name":"2023_NatureBioTech_Yeung.pdf","date_updated":"2023-08-16T11:30:45Z","checksum":"668447a1c8d360b68f8aaf9e08ed644f","file_size":12040976,"date_created":"2023-08-16T11:30:45Z","success":1,"access_level":"open_access"}],"citation":{"ama":"Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden A. scChIX-seq infers dynamic relationships between histone modifications in single cells. <i>Nature Biotechnology</i>. 2023;41:813–823. doi:<a href=\"https://doi.org/10.1038/s41587-022-01560-3\">10.1038/s41587-022-01560-3</a>","chicago":"Yeung, Jake, Maria Florescu, Peter Zeller, Buys Anton De Barbanson, Max D. Wellenstein, and Alexander Van Oudenaarden. “ScChIX-Seq Infers Dynamic Relationships between Histone Modifications in Single Cells.” <i>Nature Biotechnology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41587-022-01560-3\">https://doi.org/10.1038/s41587-022-01560-3</a>.","ista":"Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden A. 2023. scChIX-seq infers dynamic relationships between histone modifications in single cells. Nature Biotechnology. 41, 813–823.","ieee":"J. Yeung, M. Florescu, P. Zeller, B. A. De Barbanson, M. D. Wellenstein, and A. Van Oudenaarden, “scChIX-seq infers dynamic relationships between histone modifications in single cells,” <i>Nature Biotechnology</i>, vol. 41. Springer Nature, pp. 813–823, 2023.","short":"J. Yeung, M. Florescu, P. Zeller, B.A. De Barbanson, M.D. Wellenstein, A. Van Oudenaarden, Nature Biotechnology 41 (2023) 813–823.","mla":"Yeung, Jake, et al. “ScChIX-Seq Infers Dynamic Relationships between Histone Modifications in Single Cells.” <i>Nature Biotechnology</i>, vol. 41, Springer Nature, 2023, pp. 813–823, doi:<a href=\"https://doi.org/10.1038/s41587-022-01560-3\">10.1038/s41587-022-01560-3</a>.","apa":"Yeung, J., Florescu, M., Zeller, P., De Barbanson, B. A., Wellenstein, M. D., &#38; Van Oudenaarden, A. (2023). scChIX-seq infers dynamic relationships between histone modifications in single cells. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-022-01560-3\">https://doi.org/10.1038/s41587-022-01560-3</a>"},"oa_version":"Published Version","scopus_import":"1","language":[{"iso":"eng"}],"volume":41,"year":"2023","publisher":"Springer Nature","pmid":1},{"date_published":"2023-02-01T00:00:00Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"day":"01","quality_controlled":"1","oa":1,"month":"02","date_updated":"2025-04-23T08:45:00Z","intvolume":"        55","acknowledgement":"We thank A. Giladi for sharing mRNA abundance tables of cell types together with J. van den Berg for critical reading of the manuscript. We thank M. Bartosovic for sharing method comparison data. pK19pA-MN was a gift from Ulrich Laemmli (Addgene plasmid 86973, http://n2t.net/addgene:86973; RRID:Addgene_86973). Figure 8 is adopted from Hematopoiesis (human) diagram by A. Rad and M. Häggström under CC-BY-SA 3.0 license. This work was supported by European Research Council Advanced under grant ERC-AdG 742225-IntScOmics and Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP award NWO-CW 714.016.001. The SNF (P2BSP3-174991), HFSP (LT000209/2018-L) and Marie Skłodowska-Curie Actions (798573) supported P.Z. The SNF (P2ELP3_184488) and HFSP (LT000097/2019-L) supported J.Y. and the EMBO LTF (ALTF 1197–2019) supported V.B. This work is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","file_date_updated":"2023-02-27T07:46:45Z","abstract":[{"lang":"eng","text":"Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages."}],"type":"journal_article","article_type":"review","page":"333-345","author":[{"full_name":"Zeller, Peter","last_name":"Zeller","first_name":"Peter"},{"last_name":"Yeung","orcid":"0000-0003-1732-1559","full_name":"Yeung, Jake","id":"123012b2-db30-11eb-b4d8-a35840c0551b","first_name":"Jake"},{"first_name":"Helena","full_name":"Viñas Gaza, Helena","last_name":"Viñas Gaza"},{"first_name":"Buys Anton","full_name":"de Barbanson, Buys Anton","last_name":"de Barbanson"},{"last_name":"Bhardwaj","full_name":"Bhardwaj, Vivek","first_name":"Vivek"},{"first_name":"Maria","last_name":"Florescu","full_name":"Florescu, Maria"},{"last_name":"van der Linden","full_name":"van der Linden, Reinier","first_name":"Reinier"},{"first_name":"Alexander","last_name":"van Oudenaarden","full_name":"van Oudenaarden, Alexander"}],"date_created":"2023-01-12T12:09:09Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12158","status":"public","article_processing_charge":"No","department":[{"_id":"ScienComp"}],"doi":"10.1038/s41588-022-01260-3","ddc":["570","000"],"has_accepted_license":"1","publication_status":"published","title":"Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis","external_id":{"pmid":["36539617"]},"publication_identifier":{"eissn":["1546-1718"],"issn":["1061-4036"]},"publication":"Nature Genetics","pmid":1,"keyword":["Genetics"],"year":"2023","publisher":"Springer Nature","language":[{"iso":"eng"}],"volume":55,"fulldoi":"https://doi.org/10.1038/s41588-022-01260-3","file":[{"content_type":"application/pdf","file_id":"12688","relation":"main_file","creator":"dernst","checksum":"6fdb8e34fbeea63edd0f2c6c2cc5823e","file_size":21484855,"date_updated":"2023-02-27T07:46:45Z","file_name":"2023_NatureGenetics_Zeller.pdf","success":1,"date_created":"2023-02-27T07:46:45Z","access_level":"open_access"}],"citation":{"ieee":"P. Zeller <i>et al.</i>, “Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis,” <i>Nature Genetics</i>, vol. 55. Springer Nature, pp. 333–345, 2023.","ista":"Zeller P, Yeung J, Viñas Gaza H, de Barbanson BA, Bhardwaj V, Florescu M, van der Linden R, van Oudenaarden A. 2023. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. Nature Genetics. 55, 333–345.","ama":"Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. 2023;55:333-345. doi:<a href=\"https://doi.org/10.1038/s41588-022-01260-3\">10.1038/s41588-022-01260-3</a>","chicago":"Zeller, Peter, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson, Vivek Bhardwaj, Maria Florescu, Reinier van der Linden, and Alexander van Oudenaarden. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41588-022-01260-3\">https://doi.org/10.1038/s41588-022-01260-3</a>.","short":"P. Zeller, J. Yeung, H. Viñas Gaza, B.A. de Barbanson, V. Bhardwaj, M. Florescu, R. van der Linden, A. van Oudenaarden, Nature Genetics 55 (2023) 333–345.","apa":"Zeller, P., Yeung, J., Viñas Gaza, H., de Barbanson, B. A., Bhardwaj, V., Florescu, M., … van Oudenaarden, A. (2023). Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41588-022-01260-3\">https://doi.org/10.1038/s41588-022-01260-3</a>","mla":"Zeller, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>, vol. 55, Springer Nature, 2023, pp. 333–45, doi:<a href=\"https://doi.org/10.1038/s41588-022-01260-3\">10.1038/s41588-022-01260-3</a>."},"scopus_import":"1","oa_version":"Published Version"},{"department":[{"_id":"ScienComp"}],"ddc":["000"],"doi":"10.3389/fmicb.2023.1257002","has_accepted_license":"1","title":"Advancing microbiome research with machine learning: Key findings from the ML4Microbiome COST action","publication_status":"published","external_id":{"isi":["001080536000001"],"pmid":["37808321"]},"article_number":"1257002","publication":"Frontiers in Microbiology","publication_identifier":{"eissn":["1664-302X"]},"pmid":1,"publisher":"Frontiers","year":"2023","language":[{"iso":"eng"}],"volume":14,"file":[{"creator":"dernst","relation":"main_file","file_id":"14471","content_type":"application/pdf","date_updated":"2023-10-30T13:38:48Z","file_name":"2023_FrontiersMicrobiology_DElia.pdf","checksum":"6c0acdd8fa111a699826957b8dff19d5","file_size":505078,"date_created":"2023-10-30T13:38:48Z","success":1,"access_level":"open_access"}],"fulldoi":"https://doi.org/10.3389/fmicb.2023.1257002","oa_version":"Published Version","scopus_import":"1","citation":{"ama":"D’Elia D, Truu J, Lahti L, et al. Advancing microbiome research with machine learning: Key findings from the ML4Microbiome COST action. <i>Frontiers in Microbiology</i>. 2023;14. doi:<a href=\"https://doi.org/10.3389/fmicb.2023.1257002\">10.3389/fmicb.2023.1257002</a>","chicago":"D’Elia, Domenica, Jaak Truu, Leo Lahti, Magali Berland, Georgios Papoutsoglou, Michelangelo Ceci, Aldert Zomer, et al. “Advancing Microbiome Research with Machine Learning: Key Findings from the ML4Microbiome COST Action.” <i>Frontiers in Microbiology</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fmicb.2023.1257002\">https://doi.org/10.3389/fmicb.2023.1257002</a>.","ista":"D’Elia D, Truu J, Lahti L, Berland M, Papoutsoglou G, Ceci M, Zomer A, Lopes MB, Ibrahimi E, Gruca A, Nechyporenko A, Frohme M, Klammsteiner T, Pau ECDS, Marcos-Zambrano LJ, Hron K, Pio G, Simeon A, Suharoschi R, Moreno-Indias I, Temko A, Nedyalkova M, Apostol ES, Truică CO, Shigdel R, Telalović JH, Bongcam-Rudloff E, Przymus P, Jordamović NB, Falquet L, Tarazona S, Sampri A, Isola G, Pérez-Serrano D, Trajkovik V, Klucar L, Loncar-Turukalo T, Havulinna AS, Jansen C, Bertelsen RJ, Claesson MJ. 2023. Advancing microbiome research with machine learning: Key findings from the ML4Microbiome COST action. Frontiers in Microbiology. 14, 1257002.","ieee":"D. D’Elia <i>et al.</i>, “Advancing microbiome research with machine learning: Key findings from the ML4Microbiome COST action,” <i>Frontiers in Microbiology</i>, vol. 14. Frontiers, 2023.","short":"D. D’Elia, J. Truu, L. Lahti, M. Berland, G. Papoutsoglou, M. Ceci, A. Zomer, M.B. Lopes, E. Ibrahimi, A. Gruca, A. Nechyporenko, M. Frohme, T. Klammsteiner, E.C.D.S. Pau, L.J. Marcos-Zambrano, K. Hron, G. Pio, A. Simeon, R. Suharoschi, I. Moreno-Indias, A. Temko, M. Nedyalkova, E.S. Apostol, C.O. Truică, R. Shigdel, J.H. Telalović, E. Bongcam-Rudloff, P. Przymus, N.B. Jordamović, L. Falquet, S. Tarazona, A. Sampri, G. Isola, D. Pérez-Serrano, V. Trajkovik, L. Klucar, T. Loncar-Turukalo, A.S. Havulinna, C. Jansen, R.J. Bertelsen, M.J. Claesson, Frontiers in Microbiology 14 (2023).","mla":"D’Elia, Domenica, et al. “Advancing Microbiome Research with Machine Learning: Key Findings from the ML4Microbiome COST Action.” <i>Frontiers in Microbiology</i>, vol. 14, 1257002, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fmicb.2023.1257002\">10.3389/fmicb.2023.1257002</a>.","apa":"D’Elia, D., Truu, J., Lahti, L., Berland, M., Papoutsoglou, G., Ceci, M., … Claesson, M. J. (2023). Advancing microbiome research with machine learning: Key findings from the ML4Microbiome COST action. <i>Frontiers in Microbiology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fmicb.2023.1257002\">https://doi.org/10.3389/fmicb.2023.1257002</a>"},"date_published":"2023-09-25T00:00:00Z","oa":1,"day":"25","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","month":"09","date_updated":"2023-12-13T13:07:21Z","abstract":[{"text":"The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish “gold standard” protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory ‘omics’ features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.","lang":"eng"}],"file_date_updated":"2023-10-30T13:38:48Z","acknowledgement":"This study is based upon work from COST Action ML4Microbiome “Statistical and machine learning techniques in human microbiome studies” (CA18131), supported by COST (European Cooperation in Science and Technology), www.cost.eu. MB acknowledges support through the Metagenopolis grant ANR-11-DPBS-0001. IM-I acknowledges support by the “Miguel Servet Type II” program (CPII21/00013) of the ISCIII-Madrid (Spain), co-financed by the FEDER.\r\nThe authors are grateful to all COST Action CA18131 “Statistical and machine learning techniques in human microbiome studies” members for their contribution to the COST Action objectives, and to COST (European Cooperation in Science and Technology) for the economic support, www.cost.eu. WG2 and WG3 thank Emmanuelle Le Chatelier and Pauline Barbet (Université Paris-Saclay, INRAE, MetaGenoPolis, 78350, Jouy-en-Josas, France) for preparing the shotgun CRC benchmark dataset.","intvolume":"        14","type":"journal_article","isi":1,"article_type":"original","author":[{"first_name":"Domenica","full_name":"D’Elia, Domenica","last_name":"D’Elia"},{"first_name":"Jaak","last_name":"Truu","full_name":"Truu, Jaak"},{"last_name":"Lahti","full_name":"Lahti, Leo","first_name":"Leo"},{"first_name":"Magali","full_name":"Berland, Magali","last_name":"Berland"},{"full_name":"Papoutsoglou, Georgios","last_name":"Papoutsoglou","first_name":"Georgios"},{"last_name":"Ceci","full_name":"Ceci, Michelangelo","first_name":"Michelangelo"},{"full_name":"Zomer, Aldert","last_name":"Zomer","first_name":"Aldert"},{"first_name":"Marta B.","last_name":"Lopes","full_name":"Lopes, Marta B."},{"first_name":"Eliana","full_name":"Ibrahimi, Eliana","last_name":"Ibrahimi"},{"first_name":"Aleksandra","full_name":"Gruca, Aleksandra","last_name":"Gruca"},{"last_name":"Nechyporenko","full_name":"Nechyporenko, Alina","first_name":"Alina"},{"full_name":"Frohme, Marcus","last_name":"Frohme","first_name":"Marcus"},{"last_name":"Klammsteiner","full_name":"Klammsteiner, Thomas","first_name":"Thomas"},{"last_name":"Pau","full_name":"Pau, Enrique Carrillo De Santa","first_name":"Enrique Carrillo De Santa"},{"first_name":"Laura Judith","full_name":"Marcos-Zambrano, Laura Judith","last_name":"Marcos-Zambrano"},{"first_name":"Karel","full_name":"Hron, Karel","last_name":"Hron"},{"full_name":"Pio, Gianvito","last_name":"Pio","first_name":"Gianvito"},{"last_name":"Simeon","full_name":"Simeon, Andrea","first_name":"Andrea"},{"first_name":"Ramona","last_name":"Suharoschi","full_name":"Suharoschi, Ramona"},{"first_name":"Isabel","last_name":"Moreno-Indias","full_name":"Moreno-Indias, Isabel"},{"first_name":"Andriy","last_name":"Temko","full_name":"Temko, Andriy"},{"first_name":"Miroslava","last_name":"Nedyalkova","full_name":"Nedyalkova, Miroslava"},{"last_name":"Apostol","full_name":"Apostol, Elena Simona","first_name":"Elena Simona"},{"full_name":"Truică, Ciprian Octavian","last_name":"Truică","first_name":"Ciprian Octavian"},{"last_name":"Shigdel","full_name":"Shigdel, Rajesh","first_name":"Rajesh"},{"last_name":"Telalović","full_name":"Telalović, Jasminka Hasić","first_name":"Jasminka Hasić"},{"full_name":"Bongcam-Rudloff, Erik","last_name":"Bongcam-Rudloff","first_name":"Erik"},{"first_name":"Piotr","full_name":"Przymus, Piotr","last_name":"Przymus"},{"first_name":"Naida Babić","last_name":"Jordamović","full_name":"Jordamović, Naida Babić"},{"first_name":"Laurent","last_name":"Falquet","full_name":"Falquet, Laurent"},{"first_name":"Sonia","last_name":"Tarazona","full_name":"Tarazona, Sonia"},{"last_name":"Sampri","full_name":"Sampri, Alexia","first_name":"Alexia"},{"first_name":"Gaetano","last_name":"Isola","full_name":"Isola, Gaetano"},{"last_name":"Pérez-Serrano","full_name":"Pérez-Serrano, David","first_name":"David"},{"last_name":"Trajkovik","full_name":"Trajkovik, Vladimir","first_name":"Vladimir"},{"full_name":"Klucar, Lubos","last_name":"Klucar","first_name":"Lubos"},{"full_name":"Loncar-Turukalo, Tatjana","last_name":"Loncar-Turukalo","first_name":"Tatjana"},{"first_name":"Aki S.","last_name":"Havulinna","full_name":"Havulinna, Aki S."},{"last_name":"Jansen","full_name":"Jansen, Christian","id":"837b2259-bcc9-11ed-a196-ae55927bc6e2","first_name":"Christian"},{"first_name":"Randi J.","last_name":"Bertelsen","full_name":"Bertelsen, Randi J."},{"first_name":"Marcus Joakim","last_name":"Claesson","full_name":"Claesson, Marcus Joakim"}],"date_created":"2023-10-22T22:01:16Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14449","status":"public","article_processing_charge":"Yes"},{"date_created":"2023-06-23T11:03:18Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"13162","status":"public","article_processing_charge":"No","type":"conference_abstract","conference":{"start_date":"2023-06-12","location":"Maribor, Slovenia","end_date":"2023-06-15","name":"ASHPC: Austrian-Slovenian HPC Meeting"},"corr_author":"1","page":"42-42","author":[{"id":"490F40CE-F248-11E8-B48F-1D18A9856A87","first_name":"Stefano","last_name":"Elefante","full_name":"Elefante, Stefano"},{"last_name":"Stadlbauer","full_name":"Stadlbauer, Stephan","first_name":"Stephan","id":"4D0BC184-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Alexander","full_name":"Alexander, Michael F","id":"3A02A8FA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael F"},{"orcid":"0000-0002-5621-8100","full_name":"Schlögl, 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Schlögl, S. Elefante, V.-V. Hodirnau, in:, ASHPC23 - Austrian-Slovenian HPC Meeting 2023, EuroCC Austria, 2023, pp. 59–59.","apa":"Schlögl, A., Elefante, S., &#38; Hodirnau, V.-V. (2023). Running Windows-applications on a Linux HPC cluster using WINE. In <i>ASHPC23 - Austrian-Slovenian HPC Meeting 2023</i> (pp. 59–59). Maribor, Slovenia: EuroCC Austria.","mla":"Schlögl, Alois, et al. “Running Windows-Applications on a Linux HPC Cluster Using WINE.” <i>ASHPC23 - Austrian-Slovenian HPC Meeting 2023</i>, EuroCC Austria, 2023, pp. 59–59.","ista":"Schlögl A, Elefante S, Hodirnau V-V. 2023. Running Windows-applications on a Linux HPC cluster using WINE. ASHPC23 - Austrian-Slovenian HPC Meeting 2023. ASHPC: Austrian-Slovenian HPC Meeting, 59–59.","ieee":"A. Schlögl, S. Elefante, and V.-V. Hodirnau, “Running Windows-applications on a Linux HPC cluster using WINE,” in <i>ASHPC23 - Austrian-Slovenian HPC Meeting 2023</i>, Maribor, Slovenia, 2023, pp. 59–59.","ama":"Schlögl A, Elefante S, Hodirnau V-V. Running Windows-applications on a Linux HPC cluster using WINE. In: <i>ASHPC23 - Austrian-Slovenian HPC Meeting 2023</i>. EuroCC Austria; 2023:59-59.","chicago":"Schlögl, Alois, Stefano Elefante, and Victor-Valentin Hodirnau. “Running Windows-Applications on a Linux HPC Cluster Using WINE.” In <i>ASHPC23 - Austrian-Slovenian HPC Meeting 2023</i>, 59–59. EuroCC Austria, 2023."},"oa_version":"Submitted Version","language":[{"iso":"eng"}],"year":"2023","publisher":"EuroCC Austria"},{"corr_author":"1","page":"7","author":[{"first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","last_name":"Schlögl","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois"},{"first_name":"Andrei","id":"77129392-B450-11EA-8745-D4653DDC885E","last_name":"Hornoiu","full_name":"Hornoiu, Andrei"},{"full_name":"Elefante, Stefano","last_name":"Elefante","id":"490F40CE-F248-11E8-B48F-1D18A9856A87","first_name":"Stefano"},{"last_name":"Stadlbauer","full_name":"Stadlbauer, Stephan","id":"4D0BC184-F248-11E8-B48F-1D18A9856A87","first_name":"Stephan"}],"type":"conference_abstract","conference":{"start_date":"2022-05-31","end_date":"2022-06-02","name":"ASHPC: Austrian-Slovenian HPC Meeting","location":"Grundlsee, Austria"},"status":"public","article_processing_charge":"No","date_created":"2023-05-05T09:13:42Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12894","month":"06","date_updated":"2026-07-06T13:02:13Z","date_published":"2022-06-02T00:00:00Z","oa":1,"day":"02","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"file_date_updated":"2023-05-05T09:06:00Z","acknowledgement":"The abstracts in this booklet are licenced under a CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/legalcode), except Markus Wallerberger’s contribution at page 21, licenced under a CC BY-SA 4.0 licence (https://creativecommons.org/licenses/by-sa/4.0/legalcode).\r\n","publisher":"EuroCC Austria","year":"2022","file":[{"access_level":"open_access","date_created":"2023-05-05T09:06:00Z","success":1,"date_updated":"2023-05-05T09:06:00Z","file_name":"BOOKLET_ASHPC22.pdf","file_size":7180531,"checksum":"e3f8c240b85422ce2190e7b203cc2563","creator":"schloegl","relation":"main_file","file_id":"12895","content_type":"application/pdf"}],"fulldoi":"https://doi.org/10.25365/phaidra.337","oa_version":"Published Version","citation":{"short":"A. Schlögl, A. Hornoiu, S. Elefante, S. Stadlbauer, in:, ASHPC22 - Austrian-Slovenian HPC Meeting 2022, EuroCC Austria, 2022, p. 7.","mla":"Schlögl, Alois, et al. “Where Is the Sweet Spot? A Procurement Story of General Purpose Compute Nodes.” <i>ASHPC22 - Austrian-Slovenian HPC Meeting 2022</i>, EuroCC Austria, 2022, p. 7, doi:<a href=\"https://doi.org/10.25365/phaidra.337\">10.25365/phaidra.337</a>.","apa":"Schlögl, A., Hornoiu, A., Elefante, S., &#38; Stadlbauer, S. (2022). Where is the sweet spot? A procurement story of general purpose compute nodes. In <i>ASHPC22 - Austrian-Slovenian HPC Meeting 2022</i> (p. 7). Grundlsee, Austria: EuroCC Austria. <a href=\"https://doi.org/10.25365/phaidra.337\">https://doi.org/10.25365/phaidra.337</a>","chicago":"Schlögl, Alois, Andrei Hornoiu, Stefano Elefante, and Stephan Stadlbauer. “Where Is the Sweet Spot? A Procurement Story of General Purpose Compute Nodes.” In <i>ASHPC22 - Austrian-Slovenian HPC Meeting 2022</i>, 7. EuroCC Austria, 2022. <a href=\"https://doi.org/10.25365/phaidra.337\">https://doi.org/10.25365/phaidra.337</a>.","ama":"Schlögl A, Hornoiu A, Elefante S, Stadlbauer S. Where is the sweet spot? A procurement story of general purpose compute nodes. In: <i>ASHPC22 - Austrian-Slovenian HPC Meeting 2022</i>. EuroCC Austria; 2022:7. doi:<a href=\"https://doi.org/10.25365/phaidra.337\">10.25365/phaidra.337</a>","ieee":"A. Schlögl, A. Hornoiu, S. Elefante, and S. Stadlbauer, “Where is the sweet spot? A procurement story of general purpose compute nodes,” in <i>ASHPC22 - Austrian-Slovenian HPC Meeting 2022</i>, Grundlsee, Austria, 2022, p. 7.","ista":"Schlögl A, Hornoiu A, Elefante S, Stadlbauer S. 2022. Where is the sweet spot? A procurement story of general purpose compute nodes. ASHPC22 - Austrian-Slovenian HPC Meeting 2022. ASHPC: Austrian-Slovenian HPC Meeting, 7."},"language":[{"iso":"eng"}],"ddc":["000"],"doi":"10.25365/phaidra.337","has_accepted_license":"1","department":[{"_id":"ScienComp"}],"publication":"ASHPC22 - Austrian-Slovenian HPC Meeting 2022","publication_identifier":{"isbn":["978-3-200-08499-5"]},"title":"Where is the sweet spot? A procurement story of general purpose compute nodes","publication_status":"published"},{"keyword":["General Medicine"],"publisher":"MDPI","year":"2021","volume":2,"language":[{"iso":"eng"}],"citation":{"short":"P. Rubel, J. Fayn, P.W. Macfarlane, D. Pani, A. Schlögl, A. Värri, Hearts 2 (2021) 384–409.","apa":"Rubel, P., Fayn, J., Macfarlane, P. W., Pani, D., Schlögl, A., &#38; Värri, A. (2021). The history and challenges of SCP-ECG: The standard communication protocol for computer-assisted electrocardiography. <i>Hearts</i>. MDPI. <a href=\"https://doi.org/10.3390/hearts2030031\">https://doi.org/10.3390/hearts2030031</a>","mla":"Rubel, Paul, et al. “The History and Challenges of SCP-ECG: The Standard Communication Protocol for Computer-Assisted Electrocardiography.” <i>Hearts</i>, vol. 2, no. 3, MDPI, 2021, pp. 384–409, doi:<a href=\"https://doi.org/10.3390/hearts2030031\">10.3390/hearts2030031</a>.","ista":"Rubel P, Fayn J, Macfarlane PW, Pani D, Schlögl A, Värri A. 2021. The history and challenges of SCP-ECG: The standard communication protocol for computer-assisted electrocardiography. Hearts. 2(3), 384–409.","ieee":"P. Rubel, J. Fayn, P. W. Macfarlane, D. Pani, A. Schlögl, and A. Värri, “The history and challenges of SCP-ECG: The standard communication protocol for computer-assisted electrocardiography,” <i>Hearts</i>, vol. 2, no. 3. MDPI, pp. 384–409, 2021.","ama":"Rubel P, Fayn J, Macfarlane PW, Pani D, Schlögl A, Värri A. The history and challenges of SCP-ECG: The standard communication protocol for computer-assisted electrocardiography. <i>Hearts</i>. 2021;2(3):384-409. doi:<a href=\"https://doi.org/10.3390/hearts2030031\">10.3390/hearts2030031</a>","chicago":"Rubel, Paul, Jocelyne Fayn, Peter W. Macfarlane, Danilo Pani, Alois Schlögl, and Alpo Värri. “The History and Challenges of SCP-ECG: The Standard Communication Protocol for Computer-Assisted Electrocardiography.” <i>Hearts</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/hearts2030031\">https://doi.org/10.3390/hearts2030031</a>."},"oa_version":"Published Version","file":[{"date_created":"2024-04-09T06:49:47Z","success":1,"access_level":"open_access","relation":"main_file","creator":"dernst","file_id":"15302","content_type":"application/pdf","file_size":3539897,"checksum":"f67142b1e1e8ca5cd7a6a6798f46375e","file_name":"2021_Hearts_Rubel.pdf","date_updated":"2024-04-09T06:49:47Z"}],"fulldoi":"https://doi.org/10.3390/hearts2030031","department":[{"_id":"ScienComp"}],"has_accepted_license":"1","ddc":["610"],"doi":"10.3390/hearts2030031","title":"The history and challenges of SCP-ECG: The standard communication protocol for computer-assisted electrocardiography","publication_status":"published","publication":"Hearts","publication_identifier":{"issn":["2673-3846"]},"issue":"3","type":"journal_article","author":[{"first_name":"Paul","last_name":"Rubel","full_name":"Rubel, Paul"},{"last_name":"Fayn","full_name":"Fayn, Jocelyne","first_name":"Jocelyne"},{"first_name":"Peter W.","full_name":"Macfarlane, Peter W.","last_name":"Macfarlane"},{"full_name":"Pani, Danilo","last_name":"Pani","first_name":"Danilo"},{"first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","last_name":"Schlögl"},{"full_name":"Värri, Alpo","last_name":"Värri","first_name":"Alpo"}],"article_type":"review","page":"384-409","_id":"15285","date_created":"2024-04-03T09:03:31Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"Yes","status":"public","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"day":"24","quality_controlled":"1","date_published":"2021-08-24T00:00:00Z","date_updated":"2024-04-09T06:51:50Z","month":"08","file_date_updated":"2024-04-09T06:49:47Z","abstract":[{"lang":"eng","text":"Ever since the first publication of the standard communication protocol for computer-assisted electrocardiography (SCP-ECG), prENV 1064, in 1993, by the European Committee for Standardization (CEN), SCP-ECG has become a leading example in health informatics, enabling open, secure, and well-documented digital data exchange at a low cost, for quick and efficient cardiovascular disease detection and management. Based on the experiences gained, since the 1970s, in computerized electrocardiology, and on the results achieved by the pioneering, international cooperative research on common standards for quantitative electrocardiography (CSE), SCP-ECG was designed, from the beginning, to empower personalized medicine, thanks to serial ECG analysis. The fundamental concept behind SCP-ECG is to convey the necessary information for ECG re-analysis, serial comparison, and interpretation, and to structure the ECG data and metadata in sections that are mostly optional in order to fit all use cases. SCP-ECG is open to the storage of the ECG signal and ECG measurement data, whatever the ECG recording modality or computation method, and can store the over-reading trails and ECG annotations, as well as any computerized or medical interpretation reports. Only the encoding syntax and the semantics of the ECG descriptors and of the diagnosis codes are standardized. We present all of the landmarks in the development and publication of SCP-ECG, from the early 1990s to the 2009 International Organization for Standardization (ISO) SCP-ECG standards, including the latest version published by CEN in 2020, which now encompasses rest and stress ECGs, Holter recordings, and protocol-based trials."}],"intvolume":"         2","acknowledgement":"This research received no external funding. The authors thank the large number of researchers, engineers, cardiologists, and clinicians from academia, industry, and normalization organizations who contributed to the development and testing of the SCP-ECG standards."},{"publisher":"Elsevier","year":"2021","acknowledged_ssus":[{"_id":"SSU"}],"pmid":1,"file":[{"date_created":"2021-04-19T08:30:22Z","success":1,"access_level":"open_access","creator":"dernst","relation":"main_file","content_type":"application/pdf","file_id":"9339","date_updated":"2021-04-19T08:30:22Z","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","checksum":"2a5800d91b96d08b525e17319dcd5e44","file_size":6924738}],"project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"}],"fulldoi":"https://doi.org/10.1016/j.jneumeth.2021.109125","oa_version":"Published Version","citation":{"short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021).","mla":"Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6, 109125, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>.","apa":"Zhang, X., Schlögl, A., Vandael, D. H., &#38; Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. <i>Journal of Neuroscience Methods</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>","chicago":"Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” <i>Journal of Neuroscience Methods</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>.","ama":"Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. <i>Journal of Neuroscience Methods</i>. 2021;357(6). doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>","ista":"Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.","ieee":"X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo,” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6. Elsevier, 2021."},"scopus_import":"1","language":[{"iso":"eng"}],"volume":357,"ddc":["570"],"doi":"10.1016/j.jneumeth.2021.109125","has_accepted_license":"1","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"ec_funded":1,"article_number":"109125","publication":"Journal of Neuroscience Methods","publication_identifier":{"eissn":["1872-678X"],"issn":["0165-0270"]},"title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","publication_status":"published","external_id":{"pmid":["33711356"],"isi":["000661088500005"]},"article_type":"original","author":[{"first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","full_name":"Zhang, Xiaomin","last_name":"Zhang"},{"first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","last_name":"Schlögl"},{"full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"isi":1,"issue":"6","type":"journal_article","status":"public","article_processing_charge":"Yes (via OA deal)","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2021-04-18T22:01:39Z","_id":"9329","month":"03","date_updated":"2025-06-12T06:39:15Z","date_published":"2021-03-09T00:00:00Z","oa":1,"day":"09","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"quality_controlled":"1","file_date_updated":"2021-04-19T08:30:22Z","abstract":[{"text":"Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity.","lang":"eng"}],"acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari, Christoph Lampert, and Federico Stella for critically reading previous manuscript versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help with applying the Bayesian detection method to our data. We also thank Florian Marr for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support.","intvolume":"       357"},{"main_file_link":[{"url":"https://vsc.ac.at/fileadmin/user_upload/vsc/conferences/ashpc21/BOOKLET_ASHPC21.pdf","open_access":"1"}],"language":[{"iso":"eng"}],"citation":{"apa":"Schlögl, A., Elefante, S., Hornoiu, A., &#38; Stadlbauer, S. (2021). Managing software on a heterogenous HPC cluster. In <i>ASHPC21 – Austrian-Slovenian HPC Meeting 2021</i> (p. 5). Virtual: University of Ljubljana. <a href=\"https://doi.org/10.3359/2021hpc\">https://doi.org/10.3359/2021hpc</a>","mla":"Schlögl, Alois, et al. “Managing Software on a Heterogenous HPC Cluster.” <i>ASHPC21 – Austrian-Slovenian HPC Meeting 2021</i>, University of Ljubljana, 2021, p. 5, doi:<a href=\"https://doi.org/10.3359/2021hpc\">10.3359/2021hpc</a>.","short":"A. Schlögl, S. Elefante, A. Hornoiu, S. Stadlbauer, in:, ASHPC21 – Austrian-Slovenian HPC Meeting 2021, University of Ljubljana, 2021, p. 5.","ieee":"A. Schlögl, S. Elefante, A. Hornoiu, and S. Stadlbauer, “Managing software on a heterogenous HPC cluster,” in <i>ASHPC21 – Austrian-Slovenian HPC Meeting 2021</i>, Virtual, 2021, p. 5.","ista":"Schlögl A, Elefante S, Hornoiu A, Stadlbauer S. 2021. Managing software on a heterogenous HPC cluster. ASHPC21 – Austrian-Slovenian HPC Meeting 2021. ASHPC: Austrian-Slovenian HPC Meeting, 5.","ama":"Schlögl A, Elefante S, Hornoiu A, Stadlbauer S. Managing software on a heterogenous HPC cluster. In: <i>ASHPC21 – Austrian-Slovenian HPC Meeting 2021</i>. University of Ljubljana; 2021:5. doi:<a href=\"https://doi.org/10.3359/2021hpc\">10.3359/2021hpc</a>","chicago":"Schlögl, Alois, Stefano Elefante, Andrei Hornoiu, and Stephan Stadlbauer. “Managing Software on a Heterogenous HPC Cluster.” In <i>ASHPC21 – Austrian-Slovenian HPC Meeting 2021</i>, 5. University of Ljubljana, 2021. <a href=\"https://doi.org/10.3359/2021hpc\">https://doi.org/10.3359/2021hpc</a>."},"oa_version":"Published Version","file":[{"checksum":"ba73f85858fb9d5737ebc7724646dd45","file_size":422761,"date_updated":"2023-05-16T07:36:34Z","file_name":"2021_ASHPC_Schloegl.pdf","relation":"main_file","creator":"dernst","file_id":"12971","content_type":"application/pdf","access_level":"open_access","date_created":"2023-05-16T07:36:34Z","success":1}],"fulldoi":"https://doi.org/10.3359/2021hpc","publisher":"University of Ljubljana","year":"2021","title":"Managing software on a heterogenous HPC cluster","publication_status":"published","publication_identifier":{"isbn":["978-961-6980-77-7","978-961-6133-48-7"]},"publication":"ASHPC21 – Austrian-Slovenian HPC Meeting 2021","department":[{"_id":"ScienComp"}],"has_accepted_license":"1","ddc":["000"],"doi":"10.3359/2021hpc","_id":"12909","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2023-05-05T13:17:36Z","article_processing_charge":"No","status":"public","conference":{"location":"Virtual","end_date":"2021-06-02","name":"ASHPC: Austrian-Slovenian HPC Meeting","start_date":"2021-05-31"},"type":"conference_abstract","author":[{"orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois","last_name":"Schlögl","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois"},{"first_name":"Stefano","id":"490F40CE-F248-11E8-B48F-1D18A9856A87","last_name":"Elefante","full_name":"Elefante, Stefano"},{"last_name":"Hornoiu","full_name":"Hornoiu, Andrei","first_name":"Andrei","id":"77129392-B450-11EA-8745-D4653DDC885E"},{"full_name":"Stadlbauer, Stephan","last_name":"Stadlbauer","first_name":"Stephan","id":"4D0BC184-F248-11E8-B48F-1D18A9856A87"}],"page":"5","corr_author":"1","file_date_updated":"2023-05-16T07:36:34Z","oa":1,"day":"02","date_published":"2021-06-02T00:00:00Z","date_updated":"2026-10-14T09:47:31Z","month":"06"},{"author":[{"last_name":"Guzmán","orcid":"0000-0003-2209-5242","full_name":"Guzmán, José","first_name":"José","id":"30CC5506-F248-11E8-B48F-1D18A9856A87"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","last_name":"Schlögl","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100"},{"last_name":"Espinoza Martinez","orcid":"0000-0003-4710-2082","full_name":"Espinoza Martinez, Claudia ","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia "},{"first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0256-6529","full_name":"Zhang, Xiaomin","last_name":"Zhang"},{"first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin","last_name":"Suter"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"year":"2021","publisher":"IST Austria","type":"software","citation":{"short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, (2021).","mla":"Guzmán, José, et al. <i>How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network</i>. IST Austria, 2021, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10110\">10.15479/AT:ISTA:10110</a>.","apa":"Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &#38; Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. IST Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:10110\">https://doi.org/10.15479/AT:ISTA:10110</a>","chicago":"Guzmán, José, Alois Schlögl, Claudia  Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” IST Austria, 2021. <a href=\"https://doi.org/10.15479/AT:ISTA:10110\">https://doi.org/10.15479/AT:ISTA:10110</a>.","ama":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10110\">10.15479/AT:ISTA:10110</a>","ista":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:10110\">10.15479/AT:ISTA:10110</a>.","ieee":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021."},"fulldoi":"https://doi.org/10.15479/AT:ISTA:10110","status":"public","file":[{"success":1,"date_created":"2021-10-08T08:46:04Z","access_level":"open_access","content_type":"application/x-zip-compressed","file_id":"10114","relation":"main_file","creator":"cchlebak","date_updated":"2021-10-08T08:46:04Z","file_name":"patternseparation-main (1).zip","checksum":"f92f8931cad0aa7e411c1715337bf408","file_size":332990101}],"_id":"10110","related_material":{"record":[{"status":"public","id":"10816","relation":"used_for_analysis_in"}],"link":[{"description":"News on IST Webpage","url":"https://ist.ac.at/en/news/spot-the-difference/","relation":"press_release"}]},"date_created":"2021-10-08T06:44:22Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_updated":"2026-10-17T22:30:59Z","has_accepted_license":"1","doi":"10.15479/AT:ISTA:10110","month":"12","ddc":["005"],"tmp":{"legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html","name":"GNU General Public License 3.0","short":"GPL 3.0"},"day":"16","oa":1,"department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"date_published":"2021-12-16T00:00:00Z","abstract":[{"lang":"eng","text":"Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks."}],"file_date_updated":"2021-10-08T08:46:04Z","title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network"},{"intvolume":"       107","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari, Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp recording. We are grateful to Florian Marr for cell labeling, cell reconstruction, and technical assistance; Ben Suter for helpful discussions; Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor Asenov (Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical Facility) for efficient support.","file_date_updated":"2020-12-04T09:29:21Z","abstract":[{"text":"Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.","lang":"eng"}],"date_published":"2020-09-23T00:00:00Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"quality_controlled":"1","day":"23","oa":1,"month":"09","date_updated":"2025-04-15T08:29:03Z","date_created":"2020-08-14T09:36:05Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8261","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/the-bouncer-in-the-brain/","description":"News on IST Website"}]},"status":"public","article_processing_charge":"No","issue":"6","type":"journal_article","isi":1,"corr_author":"1","article_type":"original","page":"1212-1225","author":[{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","last_name":"Zhang","full_name":"Zhang, Xiaomin"},{"last_name":"Schlögl","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"publication_status":"published","title":"Selective routing of spatial information flow from input to output in hippocampal granule cells","external_id":{"isi":["000579698700009"],"pmid":["32763145"]},"publication_identifier":{"issn":["0896-6273"]},"publication":"Neuron","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"ec_funded":1,"doi":"10.1016/j.neuron.2020.07.006","ddc":["570"],"has_accepted_license":"1","language":[{"iso":"eng"}],"volume":107,"fulldoi":"https://doi.org/10.1016/j.neuron.2020.07.006","project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF"}],"file":[{"access_level":"open_access","date_created":"2020-12-04T09:29:21Z","success":1,"file_size":3011120,"checksum":"44a5960fc083a4cb3488d22224859fdc","file_name":"2020_Neuron_Zhang.pdf","date_updated":"2020-12-04T09:29:21Z","creator":"dernst","relation":"main_file","content_type":"application/pdf","file_id":"8920"}],"citation":{"short":"X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.","mla":"Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, pp. 1212–25, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">10.1016/j.neuron.2020.07.006</a>.","apa":"Zhang, X., Schlögl, A., &#38; Jonas, P. M. (2020). Selective routing of spatial information flow from input to output in hippocampal granule cells. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">https://doi.org/10.1016/j.neuron.2020.07.006</a>","chicago":"Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">https://doi.org/10.1016/j.neuron.2020.07.006</a>.","ama":"Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow from input to output in hippocampal granule cells. <i>Neuron</i>. 2020;107(6):1212-1225. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">10.1016/j.neuron.2020.07.006</a>","ieee":"X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information flow from input to output in hippocampal granule cells,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, pp. 1212–1225, 2020.","ista":"Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information flow from input to output in hippocampal granule cells. 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